Patent GB-1337478-A (GB)
Title: Dihydrobenzthiazine-s-dioxides and their preparation
IPC: C07D279/02
Filed: 1971-06-08
Abstract: 1337478 3,4 - Dihydro - 2H - 1,2 - benzothiazin - 2 - yl - alkanoic acid - S - dioxide derivatives RECORDATI S A CHEMICAL & PHARMACEUTICAL CO 8 June 1971 [11 June 1970] 19514/71 Heading C2C  Novel 3,4 - dihydro - 2H - 1,2 - benzothiazin- 2 - yl - alkanoic acid - S - dioxide derivatives of the general formula wherein X is a C 1-3  alkylene or alkylidene group and R is (a) a -NR<SP>1</SP>R<SP>2</SP> group, in which each of R<SP>1</SP> and R<SP>2</SP> is a hydrogen atom or a C 1-4  alkyl, C 2-4  alkenyl, C 3-4  alkynyl or phenyl group or NR<SP>1</SP>R<SP>2</SP> is a heterocyclic group or (b) a -NH-NR<SP>3</SP>R<SP>4</SP> group, in which each of R 3  and R<SP>4</SP> is a hydrogen atom or a C 1-4  alkyl or phenyl group or R<SP>3</SP> and R<SP>4</SP> together form a C 2  or C 3  alkylidene group, are prepared (i) by condensation of 3,4-dihydro-2H-1,2-benzothiazine-S-dioxide with a compound of the general formula Q-X-CO-R, wherein Q is a halogen atom or sulphonic acid radical; (ii) by condensation of the corresponding compound in which R is a halogen atom or C 1-4  alkoxy group with a compound of the general formula HR, wherein R is defined as in the first general formula above; (iii) by reaction of o-(2-chloroethyl)-benzenesulphonyl chloride with an amine of the general formula H 2 N-X-CO-R; (iv) when R is (b) above and R<SP>3</SP> and R<SP>4</SP> together form an alkylidene group, by reaction of the corresponding compound in which each of R<SP>3</SP> and R<SP>4</SP> is a hydrogen atom with an aldehyde or ketone of the general formula R<SP>5</SP> = O, wherein R<SP>6</SP> is a C 2  or C 3  alkylidene group; and (v) when R is (b) above and one of R<SP>3</SP> and R<SP>4</SP> is a C 2  or C 3  alkyl group and the other is a hydrogen atom, by hydrogenation of the corresponding product of (iv). 3,4 - Dihydro - 2H - 1,2 - benzothiazine - S- dioxide is prepared (A) by diazotization of oaminophenylacetonitrile hydrochloride in hydrochloric acid solution, treatment of the diazonium derivative with an acetic acid solution of SO 2  in the presence of Cu 2 Cl 2 , reaction of the resulting o - cyanomethyl - benzenesulphonyl chloride with ammonia and hydrogenation of the resulting o - cyanomethyl - benzenesulphonamide in an acidic medium in the presence of palladiumon-carbon ; (B) by hydrolysis of o-cyanomethylgenzenesulphonyl chloride with KOH, hydro. denation of the resulting potassium o-cyanomethyl - benzenesulphonate in an acidic medium in the presence of palladium-on-carbon and cyclization of the resulting o-(2-aminoethyl)- benzenesulphonic acid in the presence of POCl 3 ; and (c) by diazotization of o-(2-chloroethyl)- aniline hydrochloride in hydrochloric acid solution, treatment of the diazonium derivative with an acetic acid solution of SO 2  in the presence of Cu 2 Cl 2  and treatment of the resulting o - (2 - chloroethyl) - benzenesulphonyl chloride successively with ammonia and NaOH with heating. 3,4 - Dihydro - 2H - 1,2 - benzothiazin - 2 - ylalkanoic acid chloride - S - dioxides (starting materials for (ii)) are prepared by treatment of 3,4 - dihydro - 2H - 1,2 - benzo - thiazine - S- dioxide with an alkyl haloalkanoate in the presence of an alkaline agent, saponification of the resulting 3,4 - dihydro - 2H - 1,2 - benzothiazin - 2 - yl - alkanoic acid ester - S - dioxide with an alkali metal hydroxide and treatment of the resulting acid with SOCl 2